Isolation of a Breast Cancer Tumor Suppressor Gene From Chromosome 3p
Annual rept. 23 Sep 1995-22 Sep 1996
COLORADO UNIV AT DENVER
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Loss of tumor suppressor genes TSGs represent critical molecular events in the development and progression of breast cancer. Based on loss of heterozygosity LOH studies as well as direct cytogenetic studies of breast tumors, one or more TSGs most likely resides on the short arm of chromosome 3 3p and appears to be involved in nearly 50 of breast cancers. Four distinct regions within 3p P12, P14, P21 PROXIMAL AND P21 DISTAL undergo recurrent deletions in human carcinomas and are the most likely sites for a breast cancer TSG. Recently, we demonstrated recurrent homozygous deletion or rearrangement in breast cancer cell lines involving 3p14. A set of DNA clones spanning the critical region has now been sequenced revealing several potential gene coding segments. YACs containing the critical region have been modified with the Neomycin resistance gene for selective retention in mammalian cells. Introduction of YACs into a homozygously deleted breast cancer cell line should provide direct evidence concerning the presence of a functioning tumor suppressor gene. The progress made in 3p14 has now allowed us to evaluate the other candidate gene regions for involvement in breast cancer as originally proposed using deletion detection, DNA sequence analysis, gene isolation and expression assays.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research